Characterization of the antibody response against NeuGcGM3 ganglioside elicited in non-small cell lung cancer patients immunized with an anti-idiotype antibody.
1E10 mAb is an anti-Id murine mAb (Ab2 mAb) specific for an Ab1 mAb that reacts with NeuGc-containing gangliosides, sulfatides, and Ags expressed in some human tumors. In preclinical studies, this Ab2 Ab was able to mimic NeuGc-containing gangliosides only in animals lacking expression of these Ags in normal tissues. In this study, we report on the immune responses elicited in 20 non-small cell lung cancer patients treated with 1 mg of aluminum hydroxide-precipitated 1E10 mAb. In the hyperimmune sera from 16 of 20 patients, a strong specific Ab response of both IgM and IgG isotypes against NeuGcGM3 ganglioside was observed. Patient immune sera were able to induce complement-independent cell death of NeuGcGM3-expressing X63 murine myeloma target cells. Significant immunoreactivity to NeuGcGM3 was still detected after the complete abrogation of the reactivity against 1E10 mAb by the adsorption of patient sera with this Ab. We hypothesize that Id(-)Ag(+) Abs could reflect the activation of an autologous idiotypic cascade into the patients. Both Id(+)Ag(+) and Id(-)Ag(+) fractions were separated by affinity chromatography and characterized. Although IgG isotype Abs were found in both fractions, IgM isotype Abs were found only in the Id(-)Ag(+) fraction. Both Id(+)Ag(+) and Id(-)Ag(+) Abs were able to specifically recognize and induce cell death in NeuGcGM3-expressing X63 myeloma target cells. Patients that developed IgG and/or IgM Abs against NeuGcGM3 showed longer median survival times.
Hernández
Ana María
AM
Department of Antibody Engineering, Center of Molecular Immunology, Havana, Cuba. anita@ict.cim.sld.cu
Toledo
Darién
D
Martínez
Darel
D
Griñán
Tania
T
Brito
Victor
V
Macías
Amparo
A
Alfonso
Sailyn
S
Rondón
Teresa
T
Suárez
Eduardo
E
Vázquez
Ana María
AM
Pérez
Rolando
R
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000096:biosynthesis* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D000918:Antibody Specificity; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D016923:Cell Death / Q000276:immunology; D045744:Cell Line, Tumor; D004285:Dogs; D004306:Dose-Response Relationship, Immunologic; D005679:G(M3) Ganglioside / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000276:immunology; D006736:Horses; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D005679:G(M3) Ganglioside; C044298:N-glycolylneuraminyllactosylceramide